The immune response to antigen targets the effector mechanisms of the host against invading pathogens. B cell and T cell response are both profoundly modified by initial exposure to antigen and that this altered pattern can persist for years or even the lifetime of the individual provides the rationale for immunization. For the B cell, it is clear that the number of antigen reactive cells has increased many fold and that these cells are a hypermutated and antigen selected subset of the original population that makes antibody with many fold higher affinity for the antigen [1]. The circulation patterns of the cells have changed, and the population of cells, if not the cells themselves, has become long lived. The elevated number of antigen specific cells remains relatively constant over long periods in spite of a constant input and exit of large numbers of other cells from the total B cell pool. For the T cells, both CD4 and CD8, there is also an increase in frequency, a change in circulation pathways and a maintenance of memory cell numbers. For the most part, there is no mutation of receptor to molecules of higher affinity and it is not known whether there is antigen selection of cells with higher affinity receptors out of the preexisting heterogeneous pool. In many cases, for the CD4 T cell, a balance is established between the numbers of Th1 and Th2 helper T cells.Th1 and Th2 are subsets of the CD4 helper T cells and represent two populations with different patterns of cytokine secretion [2]. One population, the Th1, makes cytokines that support the activation of macrophages and are effective in the elimination of intracellular parasites such as the tubercle bacillus, while the Th2, make cytokines that support e development of antibody forming cells and the direction of immunoglobulin isotype switching to classes of antibodies most effective at dealing with parasitic infections such as helminths [3]. The dichotomy between Th1 and Th2 cells was established by in vitro studies and the contribution from CD8 T cells, rather than CD4, to a T1 versus a T2 state in vivo has not been established. It has been shown, however, the CD8 T cells can be generated as polarized effector cells and that CD8 clones reflected these two states of differentiation can be isolated from patients in various disease conditions. We define memory T cells operationally as members of an antigen specific, long lived, CD44-hi, population that can more rapidly give rise to a population of effector cells upon restimulation. We seek, in project 2, to determine the optimal conditions for the generation of stabile populations of memory CD8 T cells polarized with respect to cytokine secretion, to determine the effect of antigen on their persistence in vivo, their level of cytokine secretion and associated CTL activity. We will compare the effectiveness of T1 and T2 populations of CD8 T cells for protection against disease and the regional distribution of the T1 and T2 phenotype. Our studies will utilize mice transgenic for the T cell receptors reactive with he male HY antigen or the influenza HA antigen peptide and will involve in vitro and in vivo immunization protocols and adoptive transfer models.